Perfusion of isolated kidneys with cell free solutions leads to morphological endothelial abnormalities whether such kidneys are used for physiological studies or preservation for transplantation. We have noted massive proteinuria in isolated rat kidneys during perfusion and also in human pump-perfused cadaveric kidney recipients after implantation. These observations suggest that the morphologic endothelial abnormalities may be correlated with an abnormal permselectivity of the glomerular barrier which is manifested at least in part by proteinuria. In the isolated rat kidney, proteinuria can be partially reversed if red cells are added one hour after initiating cell free perfusion and completely prevented if red blood cells are used from the beginning of perfusion. We propose to study the effects of perfusate red blood cells and/or latex particles on glomerular ultrastructure, hemodynamics, transport of ions, protein excretion, differential permeability, and stability of the preparation by comparing perfusions in the presence or absence of particulates. The packed or particulate volume will be varied from 0.0 to 15 percent. In addition, we will verify that the effects noted are not due to oxygen carrying capacity by preincubating red blood cells with sodium nitrite or by adding carbon monoxide to the gas mixture. To test the importance of red cell deformability in mediating the effects seen, we will include norepinephrine or prostaglandins at physiologic concentrations to the perfusate. These studies are designed to provide a basis for the development of a perfusion system for the preservation of kidneys such that they manifest minimal glomerular dysfunction and morphologic change. Operating conditions of temperature, flow, pressure, ionic composition, and substrates will be tested initially in the rat kidney and then in reimplanted dog or rat kidneys. Ultimate criteria of success will be measured by function of rat or dog kidneys after ortho transplantation of kidneys which had been preserved by perfusion for variable periods of time.